Detection of aldehydes from degradation of lipid nanoparticle formulations using a hierarchically-organized nanopore electrochemical biosensor.
Biosens Bioelectron
; 261: 116457, 2024 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-38850733
ABSTRACT
Degradation of ionizable lipids in mRNA-based vaccines was recently found to deactivate the payload, demanding rigorous monitoring of impurities in lipid nanoparticle (LNP) formulations. However, parallel screening for lipid degradation in customized delivery systems for next-generation therapeutics maintains a challenging and unsolved problem. Here, we describe a nanopore electrochemical sensor to detect ppb-levels of aldehydes arising from lipid degradation in LNP formulations that can be deployed in massively parallel fashion. Specifically, we combine nanopore electrodes with a block copolymer (BCP) membrane capable of hydrophobic gating of analyte transport between the bulk solution and the nanopore volume. By incorporating aldehyde dehydrogenase (ALDH), enzymatic oxidation of aldehydes generates NADH to enable ultrasensitive voltammetric detection with limits-of-detection (LOD) down to 1.2 ppb. Sensor utility was demonstrated by detecting degradation of N-oxidized SM-102, the ionizable lipid in Moderna's SpikeVax™ vaccine, in mRNA-1273 LNP formulation. This work should be of significant use in the pharmaceutical industry, paving the way for automated on-line quality assessments of next-generation therapeutics.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Biosensing Techniques
/
Aldehydes
/
Nanoparticles
/
Electrochemical Techniques
/
Nanopores
Language:
En
Journal:
Biosens Bioelectron
Journal subject:
BIOTECNOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United kingdom